Promising biomarker for melanoma is identified

NYU School of Medicine researchers have identified a potential biomolecular marker for melanoma, the most serious form of skin cancer. In a new study, they report that the marker, a kind of molecular signature, may help identify people with melanoma who have a better prognosis and longer life-expectancy after the cancer is removed.

The study was led by Iman Osman, M.D., and David Polsky, M.D., Ph.D., who collaborated with other researchers from NYU and from Memorial Sloan-Kettering Cancer Center in New York. It will be published in the Dec. 4 issue of the Journal of the National Cancer Institute.

The researchers measured the amount of a molecule called HDM2 in tissue samples of melanoma from patients who were treated and followed at New York University Medical Center from November 1972 through November 1982. The study found that higher levels of the molecule were associated with a better prognosis; namely patients with high levels lived significantly longer after treatment than patients with low levels. And the association was maintained independent of other prognostic indicators, such as tumor thickness.

The difference between the two groups was maintained even ten years after treatment. Some 53 percent of patients with low levels had suffered a recurrence compared with 28 percent of those with high levels, according to the study. Overall, 55 percent of those with low levels had died, compared with 38 percent with high levels of the molecule.

"We think this is a promising biomarker for melanoma," says Dr. Osman, a medical oncologist. "Previously, we had determined that HDM2 was abundant in melanoma, but we didn't understand what this meant for the patient. With this retrospective study, we were able assess whether HDM2 levels at the time of diagnosis could help predict the course of the disease," she says. "The strength of our study is the large number of patients and the long-term follow-up that extends up to 18 years in some patients."

"In cancer research there is a great deal of focus on finding these kinds of molecular markers because we need more reliable means of assessing the risk of cancer recurrence," adds Dr. Polsky, a dermatologist and Associate Director of the NYU Department of Dermatology's Pigmented Lesion Section. "Our findings need to be verified independently by other groups before this marker could be used in the clinic," he says.

The researchers tracked levels of HDM2 using an antibody technique that tags the molecule with a colored stain. The molecule is involved in the pathway for a tumor suppressor gene called p53, which, when mutated, is associated with many cancers but not melanoma. It is not clear why HDM2 levels would be high in people with melanoma, says Dr. Polsky.

The incidence of melanoma continues to rise and this year it is expected to strike 53,600 people in the United States, and some 7,400 people with the disease are expected to die, according to the American Cancer Society. Melanoma is the ninth most common cancer in the United States. Excessive exposure to sunlight, a fair complexion, and a family history of melanoma, among other factors, place people at higher risk for the disease. With early detection and treatment, melanoma is highly curable.

Currently, the thickness of a melanoma at the time of diagnosis, sometimes combined with a procedure called sentinel node biopsy, is used to assess whether a patient's tumor will recur and if additional treatment with immunotherapy is warranted after the cancer is removed. Patients with early stage melanoma, called stage I cancer, have the thinnest lesions and are therefore the least likely to have a recurrence of their original cancer.

The prognosis usually worsens as the tumor extends deeper into the skin. However, levels of HDM2 in the study did not correlate with tumor thickness. "Tumor thickness is not enough," says Dr. Osman. "Two people with the same tumor thickness under the microscope may require different treatment. This is the reason why better markers can help us refine therapy."

The new study involved 134 patients with stage I, II, and III melanomas. These patients were enrolled in the Melanoma Cooperative Group at New York University Medical Center, which documented important characteristics of each patient's original tumor, such as its location and thickness. After treatment, the patients were followed for many years.

A new, prospective NYU-Interdisciplinary Melanoma Cooperative Group has been accruing patients for a new study that will track HDM2 and other molecules in tumor material. Dr. Osman, who directs the project, says that 52 patients have been enrolled over the last three months as a result of the efforts of NYU physicians participating in the care of melanoma patients. One of the long-term goals of this program is to integrate the results of molecular analyses of an individual patient's tumor into his or her treatment plan.

The co-authors on the study were Kate Melzer, Carole Hazan, Hideko Kamino, Joanna Spira, and Alfred Kopf from NYU; and Katherine Panageas, Klaus Busman, Maria Drobnjak, Carlos Cordon-Cardo, and Alan Houghton from Memorial Sloan-Kettering Cancer Center in New York City.

The study was supported by grants from the American Skin Association and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.